Age-related subcortical gray matter atrophy, ventricular dilatation, and the expansion of peripheral cerebrospinal fluid (CSF) volume was found in healthy men using magnetic resonance imaging (MRI), employing a threshold technique which allows quantification of brain matter and CSF volume changes. MRI showed a significant age related decrease of posterior frontal, but not of temporal lobe volume in healthy men. Men with mild DAT had significantly less brain matter than did healthy age-matched controls. Discriminant analysis of volumetric MRI images allowed complete separation between DAT patients and healthy age- and sex-matched controls, including validation on a separate group of mildly demented patients. Mean volumes of both the lateral ventricles were significantly larger in the neurologically and cognitively normal hypertensives as compared to controls using MRI, suggesting that longstanding hypertension results in greater ventricular enlargement than would be expected on the basis of age alone. Volumetric analysis of MRI images in Turner's syndrome (TS) revealed smaller hippocampi, basal ganglia and parieto-occipital brain matter than matched controls. Hippocampal volumes and memory test scores were reduced independently of 'X chromosome dosage' in all TS subjects, suggesting a role for sex steroids in development and death of hippocampal neurons. 31P spectra, multisection hydrogen images (to quantitate cerebral atrophy), and fluorodeoxyglucose positron emission tomographic (PET) scans were obtained from DAT patients and healthy age-matched controls. Phosphorus metabolite concentrations did not differ between patients and controls; glucose metabolic rates were reduced in DAT patients relative to controls, suggesting that disturbances in cellular phosphate energy reserves and membrane phosphoester metabolite levels do not play a major role in the neuropathology of DAT, at least in bulk regions of the brain.